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Binap, (A+-)- → 1,1-Dimethylethyl 4-(6-chloro-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 2061472
Notes
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Reaction equation

HRID 2061472 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:12].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:8][C:6]1[CH:5]=[C:4]([F:9])[C:3]2[NH:10][C:11](=[O:12])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:2]=2[CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 634876Binap, (A+-)-HCID 596832771,1-Dimethylethyl 4-({[(2-bromo-4-chloro-6-fluorophenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate

Product 1

HCID 596832761,1-Dimethylethyl 4-(6-chloro-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Under an argon atmosphere, 1,1-dimethylethyl 4-({[(2-bromo-4-chloro-6fluorophenyl)amino]carbonyl}amino)-1-piperidinecarboxylate (D7) (1.09 mmol, 0.493 g), 1,4-dioxane (4.4 ml), Pd2 dba3 (0.05 eq., 0.054 mmol, 50 mg), BINAP (0.055 eq., 0.059 mmol, 37 mg), NatBuO (1.5 eq., 1.63 mmol, 157 mg) were mixed together and heated to 80° C. under argon for 4 days. The reaction mixture was cooled to room temperature, quenched with water and the aqueous solution obtained was extracted with ethyl acetate. The solvent was evaporated and the crude was purified by MDAP. Fractions were collected and the solvent evaporated to yield the title compound, 15 mg, 3%, M+−H=368.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water
  3. customthe aqueous solution obtained
  4. extractionwas extracted with ethyl acetate
  5. customThe solvent was evaporated
  6. customthe crude was purified by MDAP
  7. customFractions were collected
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-01cd19f9c8c44a73a63aea8453ad8e83
Source dataset
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08283364B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes